Automated commercial synthesis system for preparation of O‐(2‐[18F]fluoroethyl)‐L‐tyrosine by direct nucleophilic displacement on a resin column

A slightly modified automated commercial synthesis system for preparation of O‐(2‐[¹⁸F]fluoroethyl)‐l‐tyrosine (FET), an amino acid tracer for tumor imaging with positron emission tomography, is described. Direct nucleophilic fluorination of [¹⁸F]fluoride with 1,2‐di(4‐methylphenylsulfonyloxy)ethane on a quaternary 4‐(4‐methylpiperidinyl)‐pyridinium functionalized polystyrene anion exchange resin gave 1‐[¹⁸F]‐2‐(4‐methylphenylsulfonyloxy)ethane, then [¹⁸F]fluoroalkylation of l‐tyrosine yielded FET. The overall radiochemical yield with no decay correction was about 8–10%, the whole synthesis time was about 52 min, and the radiochemical purity was above 95%. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of a phenolic precursor and its efficient O‐[18F]fluoroethylation with purified no‐carrier‐added [18F]2‐fluoroethyl brosylate as the labeling agent

[¹⁸F]2‐Fluoroethyl‐p‐toluenesulfonate also called [¹⁸F]2‐fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [¹⁸F]2‐Fluoroethyl‐4‐bromobenzenesulfonate, also called [¹⁸F]2‐fluoroethyl brosylate ([¹⁸F]F(CH₂)₂OBs), was used as an alternative radiolabeling agent to prepare [¹⁸F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O‐fluoroethylating the phenolic precursor. Purified by reverse‐phase HPLC, the no‐carrier‐added [¹⁸F]F(CH₂)₂OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [¹⁸F]F(CH₂)₂OBs with the phenolic precursor was performed by heating in DMF and successfully produced [¹⁸F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.     

Alternative solvents for electrophilic synthesis of 6‐[18F]fluoro‐L‐DOPA

Owing to the ozone layer‐depleting properties of chlorofluorocarbon compounds, alternative solvents for electrophilic fluorination reactions are desirable. Chloroform, dichloromethane, acetone or their deuterated analogues were examined as substitutes for Freon‐11 in the electrophilic synthesis of 6‐[¹⁸F]fluoro‐L ‐DOPA ([¹⁸F]FDOPA). CDCl₃, CD₂Cl₂ and C₃D₆O were found to be suitable solvents in this reaction, with the deuterated solvents providing significantly higher yields than Freon‐11. There were no differences among the solvents in the specific radioactivity, the radiochemical purity, the chemical purity or the microbiological quality of the final product. However, the radiochemical yield of [¹⁸F]FDOPA was increased when acetic acid was added to the precursor solution prior to the fluorination reaction. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of 2‐[18F]fluoroadenosine (2‐[18F]FAD) as potential radiotracer for studying malignancies by PET

2‐[¹⁸F]fluoroadenosine (2‐[¹⁸F]FAD), a potential radioligand for assessment of adenylate metabolism, was synthesized by carrier‐added and no‐carrier‐added procedures via nucleophilic radiofluorination of 2‐fluoroadenosine and 2‐iodoadenosine. The radiochemical yield, specific radioactivity and radiochemical purity of carrier‐added and no‐carrier‐added 2‐[¹⁸F]FAD were 5%, 22–30 mCi/µmol and 99%, and 0.5%, 1200–1700 mCi/µmol and 99%, respectively. Copyright © 2006 John Wiley & Sons, Ltd.     

Application of n.c.a. 4‐[18F]fluorophenol in diaryl ether syntheses of 2‐(4‐[18F]fluorophenoxy)‐benzylamines

The availability of no‐carrier‐added (n.c.a.) 4‐[¹⁸F]fluorophenol offers the possibility of introducing the 4‐[¹⁸F]fluorophenoxy moiety into potential radiopharmaceuticals. Besides alkyl–aryl ether synthesis using n.c.a. 4‐[¹⁸F]fluorophenol the diaryl ether coupling is an attractive synthetic method to enlarge the spectrum of interesting labelling procedures. As examples the syntheses of n.c.a. 2‐(4‐[¹⁸F]fluorophenoxy)‐N,N‐dimethylbenzylamine and n.c.a. 2‐(4‐[¹⁸F]fluorophenoxy)‐N‐methylbenzylamine were realized by an Ullmann ether synthesis of corresponding 2‐bromobenzoic acid amides using tetrakis(acetonitrile)copper(I) hexafluorophosphate as catalyst and a subsequent reduction of the amides formed. The radiochemical yield of the coupling varied between 5 and 65% based on labelled 4‐[¹⁸F]fluorophenol. Both compounds are structural analogues of recently published radiotracers for imaging the serotonin reuptake transporter sites (SERT). However, in vitro binding assays of both molecules showed only a low affinity towards monoamine transporters. Copyright © 2004 John Wiley & Sons, Ltd.     

An improved radiosynthesis of O‐(2‐[18F]fluoroethyl)‐O‐(p‐nitrophenyl)methylphosphonate: A first‐in‐class cholinesterase PET tracer

O‐(2‐Fluoroethyl)‐O‐(p‐nitrophenyl) methylphosphonate 1 is an organophosphate cholinesterase inhibitor that creates a phosphonyl‐serine covalent adduct at the enzyme active site blocking cholinesterase activity in vivo . The corresponding radiolabeled O‐(2‐[¹⁸F]fluoroethyl)‐O‐(p‐nitrophenyl) methylphosphonate, [ ¹⁸ F]1 , has been previously prepared and found to be an excellent positron emission tomography imaging tracer for assessment of cholinesterases in live brain, peripheral tissues, and blood. However, the previously reported [ ¹⁸ F]1 tracer synthesis was slow even with microwave acceleration, required high‐performance liquid chromatography separation of the tracer from impurities, and gave less optimal radiochemical yields. In this paper, we report a new synthetic approach to circumvent these shortcomings that is reliant on the facile reactivity of bis‐(O,O‐p‐nitrophenyl) methylphosphonate, 2 , with 2‐fluoroethanol in the presence of DBU. The cold synthesis was successfully translated to provide a more robust radiosynthesis. Using this new strategy, the desired tracer, [ ¹⁸ F]1 , was obtained in a non‐decay–corrected radiochemical yield of 8 ± 2% (n = 7) in >99% radiochemical and >95% chemical purity with a specific activity of 3174 ± 345 Ci/mmol (EOS). This new facile radiosynthesis routinely affords highly pure quantities of [ ¹⁸ F]1 , which will further enable tracer development of OP cholinesterase inhibitors and their evaluation in vivo .     

Radiosynthesis of 3‐(2′‐[18F]fluoro)‐flumazenil ([18F]FFMZ)

Recently, two fluorine‐18 labelled derivatives of flumazenil were described: 5‐(2′‐[¹⁸F]fluoroethyl)‐5‐desmethylflumazenil (ethyl 8‐fluoro‐5‐[¹⁸F]fluoroethyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylate; [¹⁸F]FEFMZ) and 3‐(2′‐[¹⁸F]fluoro)‐flumazenil (2′‐[¹⁸F]fluoroethyl 8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a]‐[1,4]diazepine‐3‐carbo‐ xylate; [¹⁸F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [¹⁸F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two‐step procedure was developed: First, [¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2‐bromo‐[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, distilled [¹⁸F]BFE was reacted with the tetrabutylammonium salt of 3‐desethylflumazenil (8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylic acid) to yield [¹⁸F]FFMZ. The synthesis of [¹⁸F]FFMZ allows for the production of up to 7 GBq of this PET‐tracer, enough to serve several patients. [¹⁸F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.     

Radiosynthesis of 4‐[18F]fluoromethyl‐L‐phenylalanine and [18F]FET via a same strategy and automated synthesis module

Currently there is still a need for more potent amino acid analogues as tumour imaging agents for peripheral tumour imaging with PET as it was recently reported that the success of O‐(2′‐[¹⁸F]fluoroethyl)‐L ‐tyrosine ([¹⁸F]FET) is limited to brain, head and neck tumours. As the earlier described 2‐Amino‐3‐(2‐[¹⁸F]fluoromethyl‐phenyl)‐propionic acid (2‐[¹⁸F]FMP) suffered from intramolecular‐catalysed defluorination, we synthesized 2‐Amino‐3‐(4‐[¹⁸F]fluoromethyl‐phenyl)‐propionic acid (4‐[¹⁸F]FMP) as an alternative for tumour imaging with PET. Radiosynthesis of 4‐[¹⁸F]FMP, based on Br for [¹⁸F] aliphatic nucleophilic exchange, was performed with a customized modular Scintomics automatic synthesis hotbox^three system in a high overall yield of 30% and with a radiochemical purity of \gt 99%. 4‐[¹⁸F]FMP was found to be stable in its radiopharmaceutical formulation, even at high radioactivity concentrations. Additionally, for a comparative study, [¹⁸F]FET was synthesized using the same setup in 40% overall yield, with a radiochemical purity \gt 99%. The described automated radiosynthesis allows the production of two different amino acid analogues with minor alternations to the parameter settings of the automated system, rendering this unit versatile for both research and clinical practice. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of [18F]fluoroacetaldehyde. Application to [18F]fluoroethylation of benzylamine under reductive alkylation conditions

The radiosynthesis of a new [¹⁸F]fluoroalkylating agent, [¹⁸F]fluoroacetaldehyde, is described. It was produced using the Kornblum method by oxidation with dimethyl sulphoxide of 2‐[¹⁸F]fluoroethyl p‐toluenesulphonate ([¹⁸F]FETos). In these conditions the oxidation proceeds smoothly and rapidly to the selective conversion of tosyl esters of primary alcohols to aldehydes with no carboxylic acids being produced. The chemical identity of [¹⁸F]fluoroacetaldehyde was determined by comparing its chromatographic properties as well as those of its 2,4‐dinitrophenylhydrazone (2,4‐DNPH) derivative with those of, respectively, the standard fluoroacetaldehyde and its 2,4‐DNPH derivative. Standard fluoroacetaldehyde was prepared by oxidation of fluoroethanol with pyridinium dichromate and characterized as its 2,4‐DNPH derivative by mass spectrometry. To test its reactivity with amines under reductive alkylation conditions, [¹⁸F]fluoroacetaldehyde was reacted with benzylamine used as model substrate. The chemical identity of the resulting radiolabelled product was determined to be [¹⁸F]N‐(2‐fluoroethyl)‐benzylamine by comparing its chromatographic properties with those of the synthesized standard N‐(2‐fluoroethyl)‐benzylamine characterized by ¹⁹F and ¹H NMR spectroscopy and mass spectrometry. This new fluorine‐18 labelled synthon may find applications in radiolabelling peptide, protein and antibody fragments as well as in aldol condensation or in the Mannich reaction. Copyright © 2008 John Wiley & Sons, Ltd.     

Automated production at the curie level of no‐carrier‐added 6‐[18F]fluoro‐ l‐dopa and 2‐[18F]fluoro‐ l‐tyrosine on a FASTlab synthesizer

An efficient, fully automated, enantioselective multi‐step synthesis of no‐carrier‐added (nca) 6‐[¹⁸F]fluoro‐L‐dopa ([¹⁸F]FDOPA) and 2‐[¹⁸F]fluoro‐L‐tyrosine ([¹⁸F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high‐ performance liquid chromatography (HPLC) purification has been developed. A PTC (phase‐transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand‐alone HPLC. [¹⁸F]FDOPA and [¹⁸F]FTYR were produced in 36.3 ± 3.0 % (n = 8) and 50.5 ± 2.7 % (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95 %, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [¹⁸F]FDOPA and [¹⁸F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.     

Automated synthesis of N‐(2‐[18F]Fluoropropionyl)‐l‐glutamic acid as an amino acid tracer for tumor imaging on a modified [18F]FDG synthesis module

N‐(2‐[¹⁸F]Fluoropropionyl)‐l ‐glutamic acid ([¹⁸F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography. However, due to the complicated multistep synthesis, the routine production of [¹⁸F]FPGLU presents many challenging laboratory requirements. To simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [¹⁸F]FPGLU was performed on a modified commercial fluorodeoxyglucose synthesizer via a 2‐step on‐column hydrolysis procedure, including ¹⁸F‐fluorination and on‐column hydrolysis reaction. [¹⁸F]FPGLU was synthesized in 12 ± 2% (n = 10, uncorrected) radiochemical yield based on [¹⁸F]fluoride using the tosylated precursor 2 . The radiochemical purity was ≥98%, and the overall synthesis time was 35 minutes. To further optimize the radiosynthesis conditions of [¹⁸F]FPGLU, a brominated precursor 3 was also used for the preparation of [¹⁸F]FPGLU, and the improved radiochemical yield was up to 20 ± 3% (n  = 10, uncorrected) in 35 minutes. Moreover, all these results were achieved using the similar on‐column hydrolysis procedure on the modified fluorodeoxyglucose synthesis module.     

Synthesis of N‐(3‐[18F]Fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([18F]FP‐β‐CIT)

N‐(3‐[¹⁸F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([¹⁸F]FP‐β‐CIT) was synthesized in a two‐step reaction sequence. In the first reaction, 1‐bromo‐3‐(nitrobenzene‐4‐sulfonyloxy)‐propane was fluorinated with no‐carrier‐added fluorine‐18. The resulting product, 1‐bromo‐3‐[¹⁸F]‐fluoropropane, was distilled into a cooled reaction vessel containing 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐nortropane, diisopropylethylamine and potassium iodide. After 30 min, the reaction mixture was subjected to a preparative HPLC purification. The product, [¹⁸F]FP‐β‐CIT, was isolated from the HPLC eluent with solid‐phase extraction and formulated to yield an isotonic, pyrogen‐free and sterile solution of [¹⁸F]FP‐β‐CIT. The overall decay‐corrected radiochemical yield was 25 ± 5%. Radiochemical purity was > 98% and the specific activity was 94 ± 50 GBq/µmol at the end of synthesis. Copyright © 2006 John Wiley & Sons, Ltd.     

Simplified synthesis of N‐(3‐[18F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([18F]β‐CFT‐FP) using [18F]fluoropropyl tosylate as the labelling reagent

A synthesis method has been developed for the labelling of N‐(3‐[¹⁸F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([¹⁸F]β‐CFT‐FP), a potential radioligand for visualization of the dopamine transporters by positron emission tomography. The two‐step synthesis includes preparation of [¹⁸F]fluoropropyl tosylate and its use without purification in the fluoroalkylation of 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane (nor‐β‐CFT). The final product is purified by HPLC. Optimization of the two synthesis steps resulted in a greater than 30% radiochemical yield of [¹⁸F]β‐CFT‐FP (decay corrected to end of bombardment). The synthesis time including HPLC‐purification was approximately 90 min. The radiochemical purity of the final product was higher than 99% and the specific radioactivity at the end of synthesis was typically 20 GBq/µmol. In comparison to alkylation by [¹⁸F]fluoropropyl bromide, the procedure described here results in an improved overall radiochemical yield of [¹⁸F]β‐CFT‐FP in a shorter time. Copyright © 2005 John Wiley & Sons, Ltd.     

Fully automated synthesis and purification of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethylpiperazine

We have developed an efficient synthesis method for the rapid and high‐yield automated synthesis of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[¹⁸F]fluorobenzamido]ethylpiperazine (p‐[¹⁸F]MPPF). No‐carrier‐added [¹⁸F]F^? was trapped on a small QMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K₂CO₃ (0.7 mg). The nucleophilic [¹⁸F]fluorination was performed with 3 mg of the nitro‐precursor in DMSO (0.4 mL) at 190 °C for 20 min, followed by the preparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25 mm AcONH₄/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p‐[¹⁸F]MPPF (retention time = 9.5 min). p‐[¹⁸F]MPPF was obtained automatically with a radiochemical yield of 38.6 ± 5.0% (decay corrected, n = 5), a specific activity of 214.3 ± 21.1 GBq/µmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of 4‐[18F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions

The first application of a Sonogashira cross‐coupling reaction in ¹⁸F chemistry has been developed. The reaction was exemplified by the cross‐coupling of terminal alkynes (ethynylcyclopentyl carbinol 6 , 17α‐ethynyl‐3,17β‐estradiol 7 and 17α‐ethynyl‐3‐methoxy‐3,17β‐estradiol 8 ) with 4‐[¹⁸F]fluoroiodobenzene. 4,4′‐Diiododiaryliodonium salts were used as precursors for the synthesis of 4‐[¹⁸F]fluoroiodobenzene, enabling the convenient access to 4‐[¹⁸F]fluoroiodobenzene in 13–70% yield using conventional heating or microwave activation. The Sonogashira cross‐coupling of 4‐[¹⁸F]fluoroiodobenzene with terminal alkynes gave the corresponding 4‐[¹⁸F]fluorophenylethynyl‐substituted compounds [¹⁸F]‐9 , [¹⁸F]‐10 and [¹⁸F]‐13 in yields up to 88% within 20 min of starting from 4‐[¹⁸F]fluoroiodobenzene. Copyright © 2003 John Wiley & Sons, Ltd.     

Use of 1,8‐bis‐(dimethylamino)‐naphthalene/H18F complex as new radiofluorinating agent

Radiopharmaceuticals containing an ¹⁸F label are of increasing interest due to their utilization in PET imaging. However, the bottleneck in these applications is the limited methods available for introduction of this radionuclide into biologically interesting molecules. In this work, we have evaluated a new radiofluorination method based on the properties of the complex between 1,8‐(dimethylamino)‐naphthalene ( PS ) and [¹⁸F]–HF. The results obtained on various model substrates suggest that, in some limited cases, this new procedure can be regarded as a possible alternative to the traditional nucleophilic route using K₂₂₂/K₂CO₃ in CH₃CN. Copyright © 2004 John Wiley & Sons, Ltd.     

Radiosynthesis of O‐[11C]methyl‐L‐tyrosine and O‐[18F]Fluoromethyl‐L‐tyrosine as potential PET tracers for imaging amino acid transport

Two positron‐emitting analogues of tyrosine, O‐[¹¹C]methyl‐L ‐tyrosine and O‐[¹⁸F]fluoromethyl‐L ‐tyrosine were prepared as new tumor imaging agents. The alkylating agent, [¹¹C]methyl triflate or [¹⁸F]fluoromethyl triflate, was simply bubbled through a dimethylsulfoxide solution of L ‐tyrosine disodium salt at room temperature. After subsequent HPLC purification the labeled L ‐tyrosine analogues were obtained in decay‐corrected radiochemical yields of over 50%, based on their corresponding labeling agent, with radiochemical purities always higher than 98%. The quite straightforward preparation, together with the high radiochemical yields achieved, make both these syntheses suitable for routine production. Copyright © 2003 John Wiley & Sons, Ltd.     

Substitution‐reduction: an alternative process for the [18F]N‐(2‐fluoroethylation) of anilines

Substitution of a halo atom (chloro or bromo) in easily prepared N‐haloacetyl‐anilines with no‐carrier added (NCA) cyclotron‐produced [¹⁸F]fluoride ion (¹⁸F, t_1/2= 109.8 min; β⁺=96.9%), followed by reduction with borane–tetrahydrofuran (BH₃–THF), provides an alternative route to NCA [¹⁸F]N‐(2‐fluoroethyl)‐anilines. This two‐step and one‐pot process is rapid (～50 min) and moderately high yielding (～40% decay‐corrected radiochemical yield (RCY) overall). In the nucleophilic substitution reaction, 18‐crown‐6 is preferred to Kryptofix^® 222 as complexing agent for the solubilization of the counter‐ion (K⁺), derived from an added metal salt, in acetonitrile. Weakly basic potassium bicarbonate is preferred as the added metal salt. Inclusion of a small amount of water, equating to 4–5 molar equivalents relative to 18‐crown‐6, base or precursor (held in equimolar ratio), is beneficial in preventing the adsorption of radioactivity onto the wall of the glass reaction vessel and for achieving high RCY in the nucleophilic substitution reaction. BH₃–THF is effective for the rapid reduction of the generated [¹⁸F]N‐fluoroacetyl‐aniline to the [¹⁸F]N‐(2‐fluoroethyl)‐aniline. Copyright © 2004 John Wiley & Sons, Ltd.     

Radiosynthesis of 1‐(4‐(2‐[18F]fluoroethoxy)benzenesulfonyl)‐3‐butyl urea: a potential β‐cell imaging agent

Tolbutamide ( 1 ) is a sulfonurea agent used to stimulate insulin secretion in type 2 diabetic patients. Its analogue 1‐(4‐(2‐[¹⁸F]fluoroethoxy)benzenesulfonyl)‐3‐butyl urea ( 3 ) was synthesized in overall radiochemical yields of 45% as a potential β‐cell imaging agent. Compound 3 was synthesized by ¹⁸F‐fluoroalkylation of the corresponding hydroxy precursor ( 2 ) with 2‐[¹⁸F]fluoroethyltosylate in DMF at 120°C for 10 min followed by purification with HPLC in a synthesis time of 50 min. Insulin secretion experiments of the authentic ¹⁹F‐standard compound on rat islets showed that the compound has a similar stimulating effect on insulin secretion as that of tolbutamide ( 1 ). The partition coefficient of compound 3 between octanol/water was determined to be 1.3±0.3 (n=5). Copyright © 2002 John Wiley & Sons, Ltd.     

Synthesis,radiofluorination and first evaluation of (±)‐[18F]MDL 100907 as serotonin 5‐HT2A receptor antagonist for PET

In some psychiatric disorders 5‐HT_2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [¹¹C]MDL 100907 for PET imaging of 5‐HT_2A receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[¹⁸F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[¹⁸F]MDL 100907 was obtained with a specific activity of at least 30 GBq/µmol (EOS) and an overall radiochemical yield of 1–2%. In order to verify its binding to 5‐HT_2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5‐HT_2A receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [¹⁸F]MDL 100907 appears to be a promising new 5‐HT_2A PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.